The transient receptor potential ion channel, TRPV1 plays an essential role in the development of inflammatory thermal hyperalgesia. We investigated the dependence of inflammatory TRPV1 induction on neurotrophic factor. Rat dorsal root ganglia (DRG) neurons were classified according to immunostaining for trk-A and IB4 and the effects of antibodies against NGF or GDNF on TRPV1 expression within the groups were then analysed by immunohistochemical means. The data were compared with the time course of trophic factor expression and the effects of their antibodies on thermal hyperalgesia against radiant heat after inflammation. Although the levels of both NGF and GDNF were increased by inflammation, NGF rapidly and transiently increased whereas GDNF increased gradually over a period of approximately one week. TRPV1 expression was increased within both trk-A positive and IB4 positive neurons after inflammation. Increased TRPV1 expression within trk-A positive neurons was prevented by anti-NGF but not by anti-GDNF, whereas TRPV1 induction within the IB4 positive group was blocked by anti-GDNF but not by anti-NGF. Both antibodies prevented the short latency of withdrawing an inflamed paw from radiant heat. These results suggest that inflammation differentially increases both NGF and GDNF, which facilitate TRPV1 expression within distinctive neurons to induce thermal hyperalgesia.

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Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in various brain functions. They also are thought to play an important role in nicotine addiction of smokers. Chronic (2)-nicotine, a nAChR agonist, treatment in mice and rats elicits a dose-dependent increase in nAChRs in the brain. Upregulation of nAChRs in postmortem human brains of smokers has also been reported. However, changes in nAChRs after cigarette smoking cessation in humans are poorly understood. The aim of this study was to detect the dynamic changes of nAChRs after smoking and smoking cessation in the brains of living subjects. Methods: We performed 5-123 Iiodo-A-85380 ( 123 I-5IA) SPECT on nonsmokers and smokers (n 5 16) who had quit smoking for 4 h, 10 d, and 21 d and calculated and compared distribution volumes (Vt) of 123 I-5IA. Results: The binding potential of nAChRs (Vt of 123 I-5IA) in the brains of smokers decreased by 33.5% 6 10.5% after 4 h of smoking cessation, increased by 25.7% 6 9.2% after 10 d of smoking cessation, and decreased to the level of nonsmokers after 21 d of smoking cessation. Conclusion: Because the upregulation of the nAChRs of the smokers after chronic exposure of the nicotine was downregulated to the nonsmokers' level by around 21 d after smoking cessation, the upregulation is a temporary effect. The decrease in nicotinic receptors to nonsmoker levels may be the breaking point during the nicotine withdrawal period.

Rationale: Psoriasis (PSO) is a systemic inflammatory skin disease associated with cardiovascular disease (CVD) and lipid dysfunction. However, traditional lipid parameters have limited prognostic value whereas assessing oxidation-modified lipids (OMLs) in this inflammatory driven condition may capture additional risk. Recently, a study showed that PSO was associated with increased lipid rich coronary plaques, therefore, investigating potential relationships with OMLs may speed understanding of increased CVD in PSO. Objective: To understand whether OMLs associate with traditional lipid phenotypes, cardiometabolic disease biomarkers and total coronary plaque, with focus on non-calcified burden (NCB) by CCTA in psoriasis. Methods and Results: PSO subjects and controls (n=252) had profiling for oxidation-modified LDL, HDL, Lp(a), cholesterol efflux capacity (CEC), lipoprotein particle size and number by NMR spectroscopy and paraoxonase (PON1) activity. Blinded CCTA coronary artery disease characterization included total burden (TB), NCB and dense-calcified burden (DCB). Compared to healthy volunteers (HV), PSO subjects were older (mean age=50.1), had increased BMI and HOMA-IR. PSO subjects had increase in oxLp(a), Lp(a) and oxHDL (p<0.05 for all) with significant association of oxLDL (β=0.10, p=0.020) and oxHDL (β=−0.11, p=0.007) with NCB. Moreover, PSO subjects expressed significantly higher PON1 (kU/μl) activity compared to HV (8.55 ± 3.21 vs. 6.24 ± 3.82, p=0.01). Finally, PSO treatment was associated with a reduction in oxHDL (U/ml) (203.79 ± 88.40 vs. 116.36 ± 85.03, p<0.001) and with a concomitant decrease in NCB at one year (1.04 ± 0.44 vs. 0.95 ± 0.32, p=0.03). Conclusions: Traditional lipids did not capture risk of lipid rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxLDL and oxHDL. The PON-1 activity was increased in PSO suggesting possible compensatory anti-oxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.